Renal Flashcards
GFR
the volume of fluid filtered from the kidney’s into Bowman’s space/ unit time.
filtration rate of all functioning nephrons- gives an estimation of number of working nephrons
Can be calculated by measuring the renal clearance of any stubstance that has a steady level in the blood, is freely filtered or is not reabsorbed or secreted by renal tubules.
Renal clearance
volume of plasma completely cleared of the substance/ unit time
Creatinine clearance (CrCl)
UCr/Pcr x volume/ time
creatinine is freely filtered, it is not reabsorbed by the secreted tubules. it overestimates the GFR by 15%
can be inaccurate, under collection will have a false low CrCl and over collection will have a false high
Serum Creatinine
a poor marker for renal function as it is influenced by muscle mass
Creatinine
comes from muscular creatine and phosphocreatine converted at steady rate 2% of total creatine/day to creatinine.
creatinine is released into bloodstream and excreted exclusively by the kidney’s only
Daily creatine demand meet by diatary and de novo syntheiss, plasma level is a funciton of muscle mass
Renal disease
Etiology- Rnal- Primary kidney diseases- congenital, aquired, (glomeular/ tubulointerstitial)
- Pre-Renal- inadequte blood supply- heartfailure or low cardiac output, low renal perfusion, volume depletion, Sepsis, severe bleeding
- Post Renal( Bilateral urinary obstruction
- tumors, BPH (Prostate)
Clinical manifestations- Acute nephritic syndrome- hematuria, proteinuria,
- nephrotic syndrome- proteinuria, edema, lipiduria, hypoalbuminemia, hyperlipidemia
- asymptomatic- proteinuria, anuria, azotemia
- chronic renal failure- prolonged symptoms of urema
- UTI- bacteruria, pyuria
- Nephrolithiasis- colic, hematuria
- Renal tubular defects- With polyuria, nocturia, electrolyte disorders
Nephrotic Glomerular disease
Clinical manifestations:Heavy proteinuria, oval fat bodies, free fat droplets, few cellular elements, fatty casts, edema, lipiduria
Nephritic Glomerular disease
Clinical manifestations- Red cells, Red cell casts, Granular casts, Variable proteinuria, White blood cells., hematuria, hypertension
Primary Glomerular Diseases
Morphology- neutrophils and macrophages,
Etiology- immune mediated- unkown except for infectious agents
Pathogenesis- Immune mechanisms- antibody, cell, complement. Most are immune. Antibodies may be formed in response to endogenous antigens such as from tumor antigens or kidney antigens. they can also be formed in response to exogenous antigens such as drugs or organisms (viral or fungal). antibodies combine with antigen in periphery or insitu forming an immune complex. the immune complex formed is localized in various parts of glomerulus, this can activate the compliment and inflammatory cells. This causes injury to glomerular filtration membrane(AND)
- Non immune mechanisms- reduction of renal mass
Immune mechanisms for primary Glomerular disase
Insitu immune complex- Ag-Ab formation, fixed antigens for anti GBM (nephritis. Planted antigens(exogenous or endogenous
Circulating immune complex- endogenous antigens for DNA or exogenous antigens for infectious protein
Cytotoxic antibodies-
direct cell injury, without immune complex deposits.
cell mediated- Sensitized T cells will cause Glomeruluar injury
Activation of alternative complement- polysaccharide, endotoxin, IgA aggregates activates C3 which activates C3bBb
Non- immune mechanisms for Primary Glomerular disease
this is caused by Focal Glomeruloscerosis which. It will lead to systemic hypertension, intraglomerular hypertension, glomerular hypertorphy, these lead to mesangial cell hyperplasia/ECM deposition, intraglomerular coagulation and epithelila injury, this causes Proteinuria and Focal glomeruloscerosis.
Histological alterations of the glomeruli
diffuse- all glomeruli,
Focal- some glomeruli
global- entire glomerulus
Segmental- part of the glomerulus.
Immunofluorescence : stais for IgG IgA IgM C3 Kappa, Lambda
distribution can be along the GBM, Mesangium or both and can be patchy or diffuse, with a fine or courase grnular or lienar pattern.
Reasons not to perfomr a Kidney Biopsy
Advanced renal disase with small, echogenic kidneys or ultrasound, patient is a young child with nephrotic syndrome, clinical picture and associated systmeic findings are fairly definitive. Orthostatic proteinuria, Normal complement, normal creatinine, normal blood pressure and limited proteinuria.
Nephrotic Syndrome
Lab findings:Heavy proteinuria, hypoalbuminemia, edema, hyperlipidemia and lipiduria, NORMAL complement
Etiology: Glomerular damage causes increased permeability of glmerular capillaries to protein, this causes albumin to leave and other proteins. This will decrease the plasma oncotic pressure which causes edema, it also decreases PLASMA VOLUME, GFR, ALODSTERONE SECRETION, this causes fluid retention and edema
- hypoalbuminemia also causes compensatory synthesis of proteins by the liver which also includes lipoprotien which will cause hyperlipidemia
Pathogenesis- Immunoglobulin deposition causes membranous nephropathy
- non immunoglobulin deposition causes minimal change, FSGS, diabetic nephropathy, amyloidosis
Minimal Change disases
Epidemiology: most common disorder in children, in 15% of adults
morphology: LM- normal glomeruli, tubules, vessels
IF- no deposits
EM**** Fusion of foot processes and efacement, detachment of basement membrane
Etiology- Idoiopathic usually, may be lymphoma or renal cell carcinoma
Pathogenesis: Primary target is glomerular epithelial cells (Podocyte) results in increased glomerular permeability and subsequent massive proteinuria. NO IC deposition, non inflammotry. it is unclear but may involve ciculating glomerular permeability factors. This is because people who have transplant have recurrence of FGSG or minimal change disease
clincal features
Course:90% will have complete remission of proteinuria within 8 weeks of steroids but with frequent relapses, children 1/3 no relapse, 1/3 relapse few times, 1/3 relapse frequently
-in adults, remission and relpases
-renal failure and mortality rates are low but higher in adults.
- die to complications of Nephrotic Syndrome or therapy
Complications: tendency to progress into CRF/ESRD
Lab diagnositcs: low serum albumin, normal serum creatinine,
- Urine: proteinuria, bland urine sediment,
- normal BP, Edema (periorbital and pedal)
FSGS
Epidemiology- 10-15% idiopathic nephrotic syndrome in children, higher in adults
MorphologyLM- FSGS
IF- negative or non specific granular deposits of IgM or C3
EM- patchy fusion of the foot processes and effacement
Etiology: often idiopathic
-secondary to HIV, Morbid obesity, chronic reflux renal ablation nephropathy, heroin use, malignancies(lymphoma), glomerulonephritis, Congenital unilateral renal agenesis or aplasia
Pathogenesis- secondary- reduction in renal mass due to any renal disease, glomerular or other causes compensatory hypertrophy and hyperfiltration of remaining glomeruli to maintain FGR, intraglomerular hypertension, Hyperfiltration injury this causes Gllomerulosclerosis
Clincal features:- Present with nrephrotic syndrome: insidious onset of asymptomatic proteinuria
Course: degree of proteinuria is improtant for prognosis. persistent proteinuria and progressive decline in renal function. ESRD -5-20 years. with 50% recurrence post transplant. IgA nephropathy
Associations:Hypertension, renal insufficiency
complications:Progression to nephrotic syndrome, massive proteinuria, microscopic hematuria,
Membranous nephropathy
Morphology-LM: diffuse thickening of GBM, little increases in cellularity
- IF: fine granular deposits of IgG, C3 along the basement membrane-subepithelial
- EM- subepithelial immune complex deposits and proliferation and growth of new GBM spikes formation
Pathogenesis: localization of IC in sub epithelial zone as a result of formation IN SITU or CIRCULATIONG IC, Resembles Heymann Nephritis. (subepithelial localization) C5b-C9 insertion into podocyte cell membrane causes damaged GFM, increased permeability massive protein uria
Clinical features- Nephrotic syndrome, Microscopic hematuria (50%), Hypertension, Renal insufficiency(late), renal vein thrombosis
Associations(antigens and disorders) Idiopathic, endogenous antigens (DNA SLE/tumors) exogenous antigens,
-hep B, syphilis, malaria, captopril, mercury, gold, penicillamine
Course: 20 year follow up 25% have remission, 50% persistent proteinuria and stable or only loss of renal function 25% develop ESRD, poor prognosis for male, over 50, and greater than 10gm of proteinuria.
Heymann nephritis
animal model of human membranous nephropathy
-mice immunized with a renal apithelial antigen that develop autoantibodies IgG cross GBMs and bind to antigens on visceral epithelial cells (podocytes. the HNAC (resultant immune complex is shed into adjacent subepithelial space and produce pathological features
Diabetic nephropathy
epidemiology: leading cause of end stage renal diseases in USA 25-40% of type 1 and type 2 diabetics
Morphology- early lesions- expansion of mesangial matrix and thickening of GBM
- later lesions- diffuse glomerulosclerosis with diffuse increase in measangial matrix and diffuse thickening of GBM
- Kimmelstiel Wilson nodules. (contain lipids and fibrin
- fibrin cap and capsular drop(plasma proteins
- ischemia: causes tubular atrophy, interstitial fibrosis and hyaline ateriolsclerosis.
Etiology: adverse effects of systemic hyperglycemia
pathogenesis: hyperglycemia causes non-enzymatic glycosalation, advanced glycosylation products, increased growth factors (TGFbeta), activation of cytokines and formation of reactive O2 species. These leads to
- increased matrix formation and mesangium expansion
- increased type IV collagen, fibronectin and decreased proteoglycan heparin sulfate with thickening of GBM,
- hemodynamic changes- hyperfiltration, increased glomerular cappilary pressure, glomerular hypertrophy
- these all lead to glomerulosclerosis.
clinical presenation: nephrotic syndrome:
course: increased glomerular hydrostatic pressure, after 7-13 years, incipient nephropathy, after 10-20 years, macroalbuminuria, overt nephropathy
20+ years, presistent and progressive HTN, highly variable decline in FGR from 1-24 ml/min/year
Amyloidosis
Morphology: LM: nodular, amorphous hyaline material in the mesangiu and capillary loops, with resultant narrowing or closing of capillary lumens. IM: Congo red stain positive with apple green birefringence
EM:subendothelial and mesangial fibrils.
Etiology: deposition of amyloid fibrils that are composed of soluble proteins that have undergone misfolding resulting in formation of b-pleated sheet structrues,
-no immune or inflammatory response, damage and dysfucntion due to infilatration by amyloid fibrils and replacement of normal organ architecture with consequent loss of cellularity.
Pathogenesis: beta pleated sheets autoaggregate to from aggregates which are sistant to catabolism and removal.
- AL primary- light chain or fragment of light chain produced by abnormal plasma cells (fibrils compsoed of light chains)
- AA secondary amyloid, amyloid precursor protein is an apolipoproteind produced by the liver as an acute phase reactant in response to LONG STANDING INFECTION OR INFLAMMATION>
Clinical features- proteinurai, edema, nephrotic syndrome. Renal insufficiency , fanconi’s synrome(electrolyte abnormal)
- CVS: CM/CHF, arrythmias, heart block,
- GIT: hepatomegaly, malabsorption, bleeding,
- Neuro: ischemic stroke, neuropathy, orthostatic hypotension,
- skin: easy bruising and purpura.
Diagonsis- biopsy of organ involved
Course-Very poor, many die of end organ failure
Association- multiple myeloma(primary)
- rheumatoid arthritis, Behcet syndrome, crohn’s disease, Osteomyelitis, Tuberculosis, renal Cell carcinoma, Hodgkin’s disease. congestive heart failure
Nephtritic Syndrome
Morphology- Urine Sediment- Red blood cells and Red blood cell casts.
- granular casts
- variable proteinuria
-possibly WBC
Normal complement levels
- IgA nephropathy- Henoch-Chnolein Purpura, Alport’s syndrome (hereditary nephtritis, SLE- Class I, II, B, Benign Hematuray
IgA nephropathy
epidemiology: Most common type of glomerulonephritis, any age, peak in 2nd and 3rd decades, Asians, caucasians, rare in blacks
Morphology- LM segmental areas of increased mesangial matrix and hypercellularity
IF: Mesangial and subendothelial deposits of IgA and C3( +/- IgG, IgM
EM: mesangial and subendothelial deposits
Pathogenesis- Production of IgA class Ic mainly from mucosal immune system. supported by clinical hematuria worsens during URI or GI infections, has a predilection for mesangium. (depositions.
clinical- eipsodes of gross hematuria, persistent microscopic hematuria between episodes. non nephrotic proteinuria normal C3C4
Course- generally prolonged benign, 20% wil progres to ESRD. most restricted to kidney but can be assocated ith others
Associations- viral respiratory illness or GI illness, arthritis, vasculitis, non-thrombocytopenic purpura (HSP), hepatic Cirrrhosis, Gluten enteropathy, HIV infection. Minimal change, Membranous wegener’s, ankylosing spondylitis, small cell Carcinoma.
Post streptococcal Glomerulonephritis
Epidemiology- More common in children 6-10 years old
Morphology: LM- hypercellular glomeruli,(neutrophils and monocytes. Proliferation of mesnagial and endothelial, epithelal cells, profess is Diffuse, closure of capillary loops due to proliferationand swelling of endothelial cells and leukocytes infiltration.
IF- granular deposits of IgG and C3 in mesangium and along capillary walls
EM- electron dense deposits in sub epithelial space humps
Etiology- nephritogenic strain of b-hemolytic streptococci
Pathogenesis- usually 10 days folloing pharyngitis or 3 weeks following impetigo. due to late period of antibody formation. intially subendothelial IC depositis that causes activation of complement and influx of inflammatory cells with resultant prolifererative GN decline in GFR, Depsoits are rapidaly cleared accounting for resolution of hematuria and renal faiulre.
- later- characterisitc subepithelial HUMPS responsible for epithelial cell damage and proteinuria
- IC deposits cleared slowly and are separated from circulation by GMP limiting their clearance. This accounts for the slow rate of resolution of proteinuria.
Clinical features- Proteinuria more than 2gm/ day. Complement levels always low. .
Course: lesions begin to resolve after a month or two and usually completley rsolved over 9 months to several years. in children almost always renal function recovered (less than 1% irrevirseble renal faiulre
- long term prognosis, some develop renal insufficiency after 10-4 years after initial illnees.
- some glomeruli irreversibly damaged, results in compensatory hypefiltration in remaining glomeruli to maintain normal fGR
- Long standing increased glomerular capillary pressure eventualy results in hemodynamic mediated injury and glomerulosclerosis
diagnosis: history, clinical presentation. elevated titers for antisterptolysinO Ab or anti DNAase B, in assocation with low complement, no renal biopsy because usually gone
Membranoproliferative glomerulonephritis (MPGN)
Morphology- thickening of the basement membrane, mesangial proliferation, infiltration of inflammatory cells.
-LM- mesangial expansion and hypercellularity, thickening of capillary loops due to double countour formation “tram track” which is duplication of GBM
-EM Type 1: Subendothelial deposits( C3+ IgG)
Type 2 deposition of dense material along GBM- unknown composition (C3)
Type 3: Subendothelial, mesangial, subepithelial deposits. C3-IgG
Etiology- primary is idiopathic, secondary is underlying systemic disorder
-Type 1 most common, idiopathic is rare, secondary forms more common- Lupus, hep C, cryoglobuilnemia, endocarditis, parasitic infection.
Pathogenesis- Type 1 complement classical activation.
Type 2 alternate complement pathway. C4 levels may be nomal but C3 remains depressed for prolonge periods due to C3 nephritic factor. (IgG binds to and stabilizes C3bBb convertase which casues continuous degradation of C3
clinical- usually before age 30 shows, hematuria or proteinuria in urinalysis, acute nephritic syndrome with hematuria, hypertension and edema, recurrent episodes of gross heamturis, insideious onset of edema and nephrotic syndrome.
course: most progress towards ESRD within 10-15 years.
Rapidly progressive Glomerulonephritis (RPGN)/ Crescentic glomerulonephritis
Morphology:LM- proliferative GN with prominent Crescent formation and segmental necrosis, crescents evolve from ceullular or fibrocellular to fibrous cresecents (fibrous is irreversible.
IF: Type 1- linear staining, anti GBM disease, Goodpasture’s syndrome idiopathic
-Type 2- Granular staining- immune complex disease- SLE, post infection, IgA, henoch Schonlein (HSP), idiopathic,
Type 3 No Staining- Pauci immune GN, Wegener’s, microscopic PAN, Church strauss, Idiopathic,
rapid decline in renal fucntion with severe oliguria, three types 123, Severe glomerular injury
-proteinuria, hematuria, red blood cell casts, hypertension, edema, variable degree of oliguria
Course: 75% die or placed on dialysis, best prognosis with treatable underlying disorder or one that spontaneously remits. (post strep)
diagnosis: renal biopsy, serology needed for diagnosis
Serology- ANCA+- no extra renal disease= idiopathcicrescentric GN, Systemic necrotisizng arteritis = Microscopic polyarteritis nodosa, Pulmonary necrotizing granuloma= Wegener’s
-Anti GBM+- if lung hemorrhage= good pastures if no anti GBM
- immune complex- Anti DNA ab= SLE, Anti strep=post strep, cryoglobulins= Cryoglobulinemia
Lupus nephirits
Epidemiology- 25-50 have renal disease onset, 60% of adults with SLE develop renal disease
Morphology: type 1- minimal mesangial LM-normal, IF and EM, mesangial immune deposits.
-Type 2 mesangila proliferative- expansion and hyperceulluarity, show, is mild,
-Type 3 focal segmental proliferative LM: less than 50% glomeruli affected on Lm subendothelial and mesangial IC deposits, complement activation and influx of inflammatory cells,
-Type 4-diffuse proliferative-moe than 50% glomeruli affected on LM, marked deposition of IC subendothelial and mesangium, crescents and necrotizing lesions.
-Type 5 membranous- subepithelial immune complex deposits, diffuse thickening of GM.
Type 6 advanced sclerosing lupus nephritis- End stage. Global sclerosis in more than 905 of glomeruli, advanced interstitial fibrosis and tubular atrophy, represents healing of prior inflammatory inury and advanced stages of chronic 3, 4, 5 lupus
etiology- atuoimmune disorder of uknown etiology, , production of autoantibody with immune complex formation that may lead to chronic inflammation and tissue distruction in a variety fo organ systems .
pathogenesis: abnormal production of antibdoies for endogenous nuclear antigens (dsDNA, ANA, sm, RNA, Ro, La- immune complex is deposited in kidney with complement activation and recrutiment of inflammatory cells and tissue destruciton.
clinical features: 90% joints, 70% skin rashes, 30% discoid lesions, 40% alopecia, 60% pleura-pericardium, 50% kidney, Raynauds -20%, Mucus membrane- 15%
CNS-15%
Type2- mild, microscopic hematuria, proteinuria, nephrotic syndrome, Renal insufficiency rare.
Type 3- heamturia, nephrotic syndrome, hypertension, renal failure
type 4- Diffuse proliferative lupus nephritis- most comon and most severe,: hematuria, proteinuria, nephrotic syndrome, renal failure, low complements, high anti-DNA levels.
Type 5- nephrotic syndrome, bland urine sediment, mild renal insufficiency, normal C3C4 negative anti DNa, Ic deposits in blood vessles.
diagnosis: more than for of the following
- malar rash, discoid rash, photosensitivity, oral ulcers, non erosive arthritis, pleuropericarditis, renal disaes, neurological disorder-schizophreina/ psycchosis, hemotological disorder (Hemolytic anemia, LwWBC Lw PLT), postive LE prep, anti dsDNA ab, anti Sm, False positive for anti treponemal test, positive fluorescent antinuclear antibody test.
Benign Hypertensive nephrosclerosis:
Clinical features: Hypertension (25% ESRD)Benign as pateients are asymptomatic usually normal or slight reduced FGR
Risk factors for ESRD- Blacks, Higher blood pressure, second underlying CKD (diabetes)
Pathogenesis: Vascular: medial and intimal thickening, which is response to hemodynamic changes, hyaline arteriosclerosis due to extravasation of plasma proteins through injured endothelium
Glomerular- Global sclerosis (ischemic injury leading to nephron loss) FSGS an adaptive injury, compensatory hyperfiltration due to nephron loss,
-Tubules and insterstitium- Tubular atrophy and interstitial fibrosis. (ischemic mediated.
clinical presentation- histor of HTN, progressive elevation in serum creatinine, mild proteinuria of less than 1 g/day, no microscopic hematuria, few progressing to ESRD
Diagnosis- long standing hypertension, gland urine sediment with MILD proteinuria, Left ventricular hypertrophy, retinopathy, stroke.
Malignant hypertensive nephrosclerosis
renal disease associatied with marked increases in blood pressure generally greater than 180/120 (diastolic more than 130, most common in young black males.
etiology- preexisting essential hypertension, secondary hypertension (pheochromocytoma, primary hyperaldosteronism,)
pathogenesis: sever ehypertension leads to endothelial wall injury in arterioles and capillaries, this will cause fibrinogen, platelet deposition, plasma proteins, which causes fibrinoid necrosis and intravascular thrombosis.
Crisis- renal failure(marked proteinuria, microscopic gross heamturia, elevated creatinine, ARF) and other organs inolved, brain(nausea and vomiting, headache, encephalopathy, stroke, seizures), eye(blurry vision, loss of vision. , heart(Acute MI, Aoritc dissecion lungs(Pulmonary edema), large vessels, organ damage over hours to days. medical emergency need intravenous antihypertensive medications to avoid irreversible damage,
Thrombotic microantiopahties
HUs and TTP
HUS/TTP
Morphology-
etiology
Pathogenesis:abnormal platelet aggregation leading to thrombsis in arteriorles and capillaries throughout the body. Thrombosis in small vessels results in mechanical injury to circulating RBCs,
Clinical microvascular thrombi lead to ischemic injury to target organs in kidney brain and heart
Clinical ground and lab findings. microangiopathic hemolytic anemia, chistocytes in peripheral blood smear, thrombocytopenia, purpuric rash, acute renal failure, neurological abnormalities, headache, confusion, seizure stroke, fever.
HUS:seen in chldren one week after episode of bloody diarrhea caused by enterohemorrhagic E coli- more severe renal failure less pronounced CNS.
associated with viral infections, shigella, slamonella, drug induced with quinine, gemcitabine, cyclosporine, ticlopidine, oral contraceptives.
TTP- CNS invlovement more pronounced, renal failure less severe, assocaited with SLE, HI, Hemotalogical malignancy
Renal artery stenosis.
Etiology: Narrowing of one or both of the renal arteries, 75-90% due to occlusion by athermatous plaque, 15-25% fibromuscular dysplasia, also Takauyasu’s arteririts, aortic/renal artery dissection. prevalence increases with age.
Morphology-(ischemic nephropathy) diffuse ischemic atrophy in kidney, crowded glmeruli, atrophic tubules, interstital fibrosis, no significant arteriolosclerosis in kidney of affected RA stenosis, Arterioles protected from transmission of high pressure due to stenotic renal artery, hypertensive arteriosclerosis in contralateral kidney due to increased systemic pressure.
Diagonsis- onset of HTN in less than 35 or greater than 55, sudden onset of unctrolled HTN in previously well controlled patient, accelerated malignant hypertensions, intermittent pulmonary edema wiht normal LV function (flash pulmonary edema, acute pulmonary venous congestion or volume overload)
Labs- flank or epigastric bruit, ARF
- asymmetrical kindy sze, Renal artery doppler measurement of blood flow velocites in renal arterites to aorta is more than 3.5 MRA renal arteries, anatomical, CT angiogram: anatomical Renal arteriogram- gold standard.
-use an angioplasty and stent if you have uncontrolled hypertension, declining renal funciton and recurrent pulmonary edema.
ATN Acute tubular necrosis
Acute injury to renal tubules, causing death(necrosis) and acute renal failure
Etiology- ischemic and toxic. ARF intrinsic and pre-renal cause-
Clinical symptoms- (36 hours initiation phase) acute decline in GFR, Oliguria/anuria, serum BUN and creatinine increased
-maintenance phase- plateau of serum creatinine and BUN- lasts for days to 3 weeks(oliguria, Uremic symptoms, fluid overload, metabolic acidosis, hyperkalemia, dialysis
-recovery phase- Tubular function is restored, Increased GFR, increase urine volume, Gradual decrease in creatinine and BUN
Clinical findings- Elevated serum creatinine and BUN, metabolic acidosis, hyperkalemia, hyperphosphatemia, anemia(decrease in erythropoietin.), Hypotension, low urine output(oliguria,anuria), pericardial friction rub confusion(uremic signs)
-inschemic insult- hypotension, vasodialotry septic shock with systemic infection, - hemorrhagic shock due to gastrointestinal bleeding, hypovolemic shock due to vomiting and diarrhea
Diagnosis- muddy brown granular casts, epithelial cell casts, free epithelial cells, proteinuria, microscopic hematuria, no pyuria, urine may be normal in severe disease.
Nephorotxic- exogenous aminoglycodsides, contrast media (CT/cardiac cath) endogenous, with hemoglobinuria, myoglobinuria
